Exploring 8-benzyl pteridine-6,7-diones as inhibitors of glutamate racemase (MurI) in gram-positive bacteria.
A successful scaffold-hopping approach gave a novel series of inhibitors of bacterial glutamate racemase (MurI). Early SAR studies of the 8-benzyl pteridine-6,7-diones led to compounds with micromolar enzyme potency and antibacterial activity.
Breault
Gloria A
GA
Infection Discovery, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA. gloria.breault@astrazeneca.com
Comita-Prevoir
Janelle
J
Eyermann
Charles J
CJ
Geng
Bolin
B
Petrichko
Randy
R
Doig
Peter
P
Gorseth
Elise
E
Noonan
Brian
B
D000591:Amino Acid Isomerases / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000201:enzymology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011621:Pteridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
C534102:8-benzyl pteridine-6,7-dione; D000900:Anti-Bacterial Agents; D011621:Pteridines; D000591:Amino Acid Isomerases; C062292:glutamate racemase